(a) Field of the Invention
This invention relates to compounds that are useful in the treatment and prevention of ulcers. More particularly, this invention relates to certain 2-[(imidazo[1,2-a]pyridin-3-ylmethyl)sulfinyl]-1H-benzimidazoles that inhibit (H.sup.+ +K.sup.+)-ATPase obtained from gastric mucosa and thus inhibit acid secretion by parietal cells of the stomach through inhibition of (H.sup.30 +K.sup.+)-ATPase. For review, see, e.g., J. G. Spenney, "Biochemical Mechanisms of Acid Secretion by Gastric Parietal Cells," J. Clin. Gastro., 5 (Suppl. 1), 7-15 (1983). In addition, some of the compounds of this invention may also exert cytoprotective activity. For review of cytoprotection, see, e.g., U.S. Pat. No. 4,359,465.
(b) Prior Art
The compound of Formula (A), 2-[imidazo[1,2-a]pyridin-2-ylmethyl)sulfinyl]-1H-benzimidazole, (See Example 4 herein), has been disclosed. ##STR1## Compound (A) differs structurally from the compounds of this invention in the position of attachment of the sulfinylmethyl function to the imidazo[1,2-a]pyridine ring system. Moreover, as shown in Table I below compound (A) differs biologically from compounds of this invention in not inhibiting (H.sup.+ +K.sup.+)-ATPase activity, a biological property characteristic of the compounds of this invention.
Certain other heterocyclylalkylsulfinylbenzimidazoles have been disclosed as gastric acid secretion inhibitors. See U.S. Pat. Nos. 4,472,409, 4,394,509, 4,337,257, 4,327,102, 4,255,431, 4,045,564, and 4,045,563; British patent No. 2,134,523; German Offenlegungeschrift No. 3,415,971, and Swedish patent No. 416649. Some heterocyclylalkylsulfinylbenzimidazoles have also been disclosed as cytoprotective agents. See U.S. Pat. No. 4,359,465. Compounds of Formula (B) are illustrative of the heterocyclylalkylsulfinylbenzimidazole compounds disclosed in these patents: ##STR2## wherein R' and R" represent hydrogen, alkyl, halogen, trifluromethyl, cyano, carboxy, hydroxy, acyl, and the like; R"' represents hydrogen, alkyl, acyl, alkoxysulfonyl, and the like; and Het represents heterocyclic groups containing at least one endocyclic (ring) nitrogen. No compound disclosed in these patents includes an imidazo[1,2-a]pyridine ring system, a structural feature characteristic of the compounds of the present invention.
Heterocyclylalkylsulfinylnaphth[2,3-d]imidazoles have also been disclosed as gastric acid secretion inhibitors. See U.S. Pat. Nos. 4,248,880 and 4,182,766. The compounds disclosed in these patents are related to compounds of Formula (B), except for having a substituted naphth[2,3-d]imidazole group instead of the benzimidazole group. Similarly, other heterocyclylalkylsulfinylbenzimidazoles having a ring fused to the benzimidazole group have been disclosed as gastric acid secretion inhibitors and cytoprotective agents. See European patent application Nos. 130,729 and 127,763. The presence of the naphth[2,3-d]imidazole group and the absence of an imidazopyridine ring system distinguishes these compounds from the compounds of the present invention.
Benzylsulfinylbenzimidazoles have also been disclosed as antiulcer agents. Belgian patent No. 903,128. No compounds disclosed in the Belgian patent contain an imidazopyridine ring system, a structural feature characteristic of the compounds of this invention.